CLINICAL HANDBOOK OF SCHIZOPHRENIA

96 I. CORE SCIENCE AND BACKGROUND INFORMATIONthinking about the common course of schizophrenia throughout much of the 20th century.However, recent longitudinal neuropsychological studies of schizophrenia suggestthat, at least after the first few years from the time of symptom onset, the level of cognitivefunctioning in patients with schizophrenia (compared to the level expected amongsame-age people in the general population) remains stable. For instance, results a studyfrom a large-scale longitudinal study by Heaton and colleagues (2001) found that thelevel of cognitive deficits remains stable regardless of the specific cognitive domain examined,current age, age of illness onset, or changes in severity of positive or negative symptoms.There is some evidence, however, such as that from Harvey (2001), that a proportionof “poor outcome” chronically institutionalized older adult patients with schizophreniamay be prone to show greater than age-normal declines in cognitive functioning. The specificfactors responsible for decline in this subgroup remain an area of ongoing research.FUNCTIONAL IMPACT OF COGNITIVEDEFICITS IN SCHIZOPHRENIAThere is strong evidence that neuropsychological impairment is related to deficits in everydayfunctioning abilities among persons with schizophrenia. As shown in the classicreview of the functional outcome literature by Green (1996), level of cognitive impairmentis a stronger predictor of patients’ level of functional independence/disability thanseverity of psychopathology. Verbal, concentration, and executive functioning skills areconsistently related to activities of daily living, social skills, and benefits derived from socialskills training programs. Neuropsychological abilities have also been shown to be relatedto performance-based measures of everyday functioning and social skills amongolder patients with schizophrenia, as well as ability to manage their own medications andcapacity to consent to treatment or research.TREATMENT OF COGNITIVE DEFICITSPharmacological TreatmentsGiven the availability of pharmacotherapy for schizophrenia and its effectiveness for certainpositive symptoms, most patients receive treatment when they first report psychoticsymptoms. Since the introduction of clozapine in 1988, followed by other second-generation(or “atypical”) antipsychotic agents such as risperidone, olanzapine, quetiapine, ziprasidone,and aripiprazole, there has been some suggestion that these second-generationmedications may partially improve certain aspects of neurocognitive functioning inschizophrenia (Keefe, Silva, Perkins, & Lieberman, 1999). The question of functionallyrelevant degrees of cognitive benefit from second-generation antipsychotic medicationsremains at least partially open for debate (Gold, 2004). It is yet unclear whether thesemedications actually enhance underlying cognitive abilities or simply lack the harmfulextrapyramidal side effects associated with conventional neuroleptics, as well as the potentialadverse effects of the anticholinergic medications typically prescribed to managesuch side effects.Regardless of how the debate resolves, however, the possibility of such benefits, togetherwith the growing literature showing the importance of cognitive deficits as predictorsof functional living skills in schizophrenia (reviewed earlier), have catalyzed interestin developing new agents that directly target the cognitive symptoms of schizophrenia forintervention. For instance, Measurement and Treatment Research to Improve Cognition